CROI 2025: Where Scientific Momentum Clashes with Political Inertia
New data on lenacapavir and cabotegravir highlighted groundbreaking potential for long-acting HIV prevention- but who is going to pay for it?
At CROI 2025, a striking contradiction unfolded: the scientific promise of HIV prevention has never been stronger, yet the political and financial commitment to scaling these innovations is faltering. The cognitive dissonance was impossible to ignore. On one hand, presentations showcased major advancements in long-acting PrEP, reinvigorated primary prevention strategies, and the need to invest more resources into stopping HIV before it starts. On the other, the U.S. funding freeze on key HIV programs—most notably PEPFAR’s pause on prevention—cast a long shadow over the conference, curbing the ambition needed to fully realize these breakthroughs.
First - lets look at the big picture: As we take stock of the global HIV response in 2025, the data tell a sobering story: progress has been made, but at an unacceptable pace. As Duke Global Health Institute Director Chris Beyrer made clear in his opening plenary, we have failed to meet UNAIDS’ 2025 targets on HIV incidence and mortality, with infections declining too slowly and some regions—Eastern Europe, Central Asia, Latin America, and the Middle East—experiencing epidemic expansion.
Meanwhile, gaps in HIV treatment and prevention persist, exacerbated by shifting U.S. policies that threaten to undo decades of progress. While long-acting PrEP and injectable therapies hold promise, current global PrEP uptake lags behind need. In many regions of the world, more people continue to acquire HIV than start PrEP—a ratio of 42:1 in Eastern Europe and Central Asia alone. (see slide below) Meanwhile, the disproportionate burden of HIV among Black MSM in the U.S. remains a glaring failure, underscoring the urgent need for more targeted and community-led interventions.
Perhaps the most immediate crisis is the policy upheaval surrounding PEPFAR. A program that has saved 25 million lives and helped stabilize HIV epidemics worldwide now faces an uncertain future due to political gridlock and funding disruptions. The Trump Administration’s pausing of nearly all PEPFAR-funded prevention services could drive up new infections according to several modeling projections showcased at CROI and elsewhere. See also amfAR analysis here and our mortality analysis here.
The decision to restrict PrEP access under U.S. foreign assistance policies defies both science and morality, leaving millions vulnerable. This policy failure is even more glaring given new scientific advancements that could dramatically expand HIV prevention efforts. At CROI, new data on lenacapavir and cabotegravir showcased the groundbreaking potential of long-acting prevention strategies—innovations that should be scaling up, not facing barriers.
What’s new with LEN?
Lenacapavir (LEN) continues to demonstrate strong potential as a long-acting treatment and prevention option for HIV, with studies confirming its high viral suppression rates in heavily treatment-experienced individuals (Brunet et al., CROI, 2025) and consistent plasma concentrations above therapeutic thresholds (Le et al., CROI, 2025). New formulations show once-yearly dosing feasibility with sustained efficacy and minimal side effects (Jogiraju et al., CROI, 2025). LEN’s combination with broadly neutralizing antibodies (bNAbs) has maintained 96% viral suppression, positioning it as a potential ART alternative (Mponponsuo et al., CROI, 2025). Additionally, LEN + islatravir in a weekly regimen showed no treatment-emergent resistance, reinforcing its promise for long-term HIV management (Vanderveen et al., CROI, 2025).
In terms of real world implementation, cost-effectiveness models suggest that scaling up LEN for PrEP in South Africa could cut HIV incidence by 41% and accelerate epidemic control by a decade (Jamieson et al., CROI, 2025). The study also determined that LEN is more cost-effective than injectable cabotegravir (CAB-LA), positioning it as a promising alternative for large-scale implementation. The estimated cost-effective threshold price for LEN ranges between $32 and $59 per injection, suggesting that affordability will be a key factor in its widespread adoption. Researchers concluded that scaling up LEN PrEP could accelerate HIV elimination in South Africa by approximately 10 years, highlighting its potential to significantly alter the trajectory of the epidemic. These findings position LEN as a transformative tool in both treatment and prevention, with potential for broader rollout pending cost and implementation considerations.
What’s new with CAB-LA?
Studies presented at CROI show cabotegravir (CAB-LA) continues to demonstrate high efficacy and durability as both a long-acting treatment and prevention tool for HIV. Studies confirm that CAB-LA PrEP maintains high persistence rates, with 72% retention at 12 months in a large U.S. cohort and zero cases of HIV acquisition among users (Traeger et al., CROI, 2025). In Brazil, 83% of participants in a PrEP choice study opted for CAB-LA over oral PrEP, highlighting its acceptability among key populations (Coutinho et al., CROI, 2025). Research also shows strong effectiveness in real-world ART settings, with 95% viral suppression maintained in a U.S. cohort receiving CAB-LA + rilpivirine (Frick et al., CROI, 2025). Among pregnant and lactating people in South Africa, CAB-LA was well accepted, suggesting its potential for broader rollout in diverse populations (Wara et al., CROI, 2025).
However, cost and access remain barriers, particularly in low and middle-income countries, where a generic CAB-LA version is not expected until 2027, and high-income countries face complex healthcare logistics for implementation (Kityo et al., CROI, 2025). Additionally, structural insights into CAB resistance suggest emerging mutations could impact its long-term effectiveness, necessitating continued surveillance (Choudhuri et al., CROI, 2025). These findings reinforce CAB-LA’s role as a transformative HIV intervention, but addressing affordability and distribution hurdles is critical for its global impact.
Prevention Paradox
Despite these advancements, the lack of clear global funding commitments and political instability threatens their real-world impact. The very programs meant to ensure equitable access—like PEPFAR—are now at risk. The abrupt U.S. funding freeze has choked the ability to implement the very innovations that could transform prevention. PEPFAR’s pause on key prevention efforts, particularly its restrictions on PrEP access, threatens to erase hard-won progress and dangerously harms the communities most at risk. The evidence is clear: long-acting prevention works. But without sustained investments, these advancements risk becoming academic exercises rather than real-world solutions.
Late in December, AVAC Executive Director Mitchel Warren and I wrote an op-ed advocating for a bold new global target—putting 5 million people on long-acting PrEP by 2030. This goal is completely achievable, but only if PEPFAR’s prevention programming is fully restored and governments, funders, and industry commit to building the infrastructure to support scaling up long-acting options. Scientific breakthroughs are only as powerful as our ability to deploy them at scale and equitably.
The Trump administration now faces a choice: either let PEPFAR’s legacy crumble or seize this opportunity to lead the next phase of HIV prevention.
Rather than allowing HIV prevention to be deprioritized, the administration can make bold investments in long-acting PrEP, AI-driven service delivery enhancements, and modernized public health infrastructure. Our new Duke University report outlined five key PEPFAR reforms, including a renewed prioritization of prevention and the integration of AI to improve access, adherence, and efficiency in HIV services. By committing to these reforms, the administration can move beyond the current chaos and program disruptions and cement a leadership role in the global HIV response.
Jonathan Mann recognized that epidemics cannot be controlled rationally when human lives are not valued equally. His work underscored that respect for human dignity and social justice is fundamental not only to economic development but to the protection of public health itself. Today, as we stand at a crossroads in HIV prevention—armed with scientific breakthroughs yet constrained by political inaction—we must ask ourselves: Are we upholding Mann’s vision, or are we repeating past mistakes?
The decision to invest in prevention, scale long-acting PrEP, and restore programs like PEPFAR is not just about funding; it is about whether we will prioritize human lives equitably or allow political roadblocks to deepen disparities. The world has a choice: follow the science and fight for dignity, allow short-sighted policies to deepen inequities and prolong the epidemic. The answer will define the next chapter of the HIV response.